非甾体抗生育药的研究 Ⅲ.马兜铃次酸开环衍生物的合成及其抗生育活性
Studies On the Non-Steroidal Antifertility Agents Ⅲ.Synthesis and antifertility activity of some ring opening derivatives of aristolic acid
-
摘要: 自印度马兜铃(Aristolochia indica L.)中提得的马兜铃次酸(Aris-tolic acid)(Ⅰ)及其甲酯,经动物实验证明具有较好的抗着床和引产作用。为了寻找结构简化、活性更强的抗生育药,我们合成了马兜铃次酸开环衍生物(Ⅱ_(1-8))。鉴于对-羟基苯丙烯酸类化合物亦有抗生育作用,因此将五个苯丙烯酸型中间体作为Ⅲ_(1-5)化合物。初步药理试验表明:Ⅱ类化合物无抗着床和抗旱孕作用。化合物Ⅲ_1和Ⅲ_2分别具有显著的抗早孕和抗着床作用(P<0.01,P<0.05),Ⅲ_4兼有上述二种作用(P<0.01)。这说明菲环破裂后,抗生育活性消失,而具有苯丙烯酸型结构的中间体仍能保持抗生育作用。Abstract: It was reported that aristolic acid, an active principle isolated from the root of Aristolochia indica L. , showed anti-implantation effect in mice and abortion effect in female albino rabbits, and its methyl ester also exerted abortifacient activity in mice. In order to search for new antifertility agents with simpler structure and stronger activity, eight ring opening derivatives of aristolic acid (Ⅱ_1-8) were synthesized. All the compounds and fheiv intermediates(Ⅲ_1-5) have cis-stilbene configuration and have not been reported in literature. Considering that p-coutnaric acid also exhibited anfifertility activity, five inter- mediates with such chemical feature and the eight ring opening derivatives were subjected to Pharmacological test, none of thc compounds(Ⅱ_1-8)showed antiter- tility activity in mice. It seemed that aristolic acid lost its activity by opening the phenanthrene ring. The intermediates Ⅲ1 and Ⅲ2 exerted significant action of termination of early pregnancy and anti-implantation respectively, showed the both effects in mice.